The advent of combinatorial chemistry, and more specifically, high throughput parallel synthesis, has placed greater and greater demands on compound analysis and purification tools. Combinatorial synthesis is used to efficiently generate large numbers of unique compounds. Analysis of the composition of these samples can be done by high performance liquid chromatography (hereafter "HPLC") in combination with mass spectrometry (hereafter "MS"), whereby each fluid sample is separated into its various components as they are partitioned between the solid sorbent packing material of the chromatographic column and the carrier mobile phase. In such columns, each of the different component compounds found in each fluid sample will interact differently with the solid sorbent material contained within the chromatographic column and will accordingly take different amounts of time to pass through and be eluted out of the exit end of the column.
Typically, such liquid chromatography methods are performed in conjunction with ultraviolet (UV) or mass spectrometry-based analysis techniques as a means of identifying and isolating desired component compounds in the various fluid samples by determining exactly when such a desired component compound is eluted from the exit end of the column. Accordingly, liquid chromatography-mass spectrometry systems can be used to purify fluid samples by first separating a fluid sample into its component compounds and then collecting only the desired component compounds found therein. Unfortunately, these systems suffer from several disadvantages.
First, liquid chromatography-mass spectrometry systems have required that each fluid sample be analyzed in sequence. Parallel analysis of different fluid samples is not possible, for reasons which will be explained. Accordingly, the efficiency of combinatorial library analysis and purification is limited by the maximum speed at which the high performance liquid chromatograph-mass spectrometer (HPLC/MS) system can sequentially analyze each one of the various fluid samples so produced.
Parallel analysis of different fluid samples is not possible with existing HPLC/MS systems because the mass spectrometer will simply generate a mass spectrum reading corresponding to all of the fluid being electrosprayed or otherwise received therein at any particular moment in time. As such, the mass spectrometer cannot distinguish between parallel electrosprays of different fluid samples simultaneously received therein. Instead, should two or more parallel electrosprays enter the mass spectrometer at the same time, the mass spectrometer would simply analyze all of the various compounds found in all of the various simultaneously-received electrosprays. As such, it is not possible for the mass spectrometer to determine from which of a plurality of simultaneously-received electrosprays a particular sensed fluid compound was present.
Moreover, when performing HPLC, time is required to separate each fluid sample into its component compounds. The time required to separate each of the fluid samples must then be added together when sequentially performing liquid chromatography on a number of different fluid samples. Accordingly, a rather time-consuming process is required in which each fluid sample must be sequentially subjected to HPLC/MS.
Further, when spraying the samples into a mass spectrometer, it is preferable that as small a portion of the sample as possible be diverted into the mass spectrometer, thus conserving the majority of the fluid samples for isolation and fraction collection.